Epistemic Priority or Aims of Research? A Critique of Lexical Priority of Truth in Regulatory Science

A general criterion for distinguishing between epistemic and non-epistemic values is that the former promotes the attainment of truth whereas the latter does not. Daniel Steel (2010, 2016) is a proponent of this criterion, although it was initially proposed by McMullin (1983). There are at least two consequences of this criterion; (i) it always prioritizes epistemic values over non-epistemic values in scientific research, and (ii) it overlooks the diverse aims of science, especially the aims of regulatory or policy-oriented science. This criterion assumes the lexical priority of truth or lexical priority of evidence. This paper attempts to show a few inadequacies of this assumption. The paper also demonstrates why epistemic priority over non-epistemic values is a problematic stance and how constraining the role of non-epistemic values as ‘tiebreakers’ may undermine the diverse aims of science

Genetic recoding to dissect the roles of site-specific protein O-GlcNAcylation

ISSN:1559-744XISSN:1559-743

Corrosion inhibition capacity of two heterocyclic oximes on copper in nitric acid: electrochemical, quantum chemical and surface morphological investigations

Two heterocyclic oximes (E)-N-hydroxy-1-(pyridin-2-yl)methanimine (Hp2ylm) and (E)-N-hydroxy-1-(pyridin-3-yl)methanimine (Hp3ylm) were synthesized from pyridine-2-carbaldehyde and pyridine-3-carbaldehyde, respectively. These oximes were characterized by various spectroscopic tools like UV, IR, MASS and NMR. The inhibition capacity of these oximes against copper corrosion in 0.1 M HNO3 was determined by polarization and impedance spectroscopic studies (EIS). At all concentrations, Hp3ylm exhibited higher inhibition efficiency than Hp2ylm. Attempt was made to illustrate the mechanism of corrosion inhibition by these oximes with the help of adsorption isotherm, scanning electron microscopic (SEM) and quantum chemical studies

The UFM1 E3 ligase recognizes and releases 60S ribosomes from ER translocons

Stalled ribosomes at the endoplasmic reticulum (ER) are covalently modified with the ubiquitin-like protein UFM1 on the 60S ribosomal subunit protein RPL26 (also known as uL24) 1,2. This modification, which is known as UFMylation, is orchestrated by the UFM1 ribosome E3 ligase (UREL) complex, comprising UFL1, UFBP1 and CDK5RAP3 (ref. 3). However, the catalytic mechanism of UREL and the functional consequences of UFMylation are unclear. Here we present cryo-electron microscopy structures of UREL bound to 60S ribosomes, revealing the basis of its substrate specificity. UREL wraps around the 60S subunit to form a C-shaped clamp architecture that blocks the tRNA-binding sites at one end, and the peptide exit tunnel at the other. A UFL1 loop inserts into and remodels the peptidyl transferase centre. These features of UREL suggest a crucial function for UFMylation in the release and recycling of stalled or terminated ribosomes from the ER membrane. In the absence of functional UREL, 60S–SEC61 translocon complexes accumulate at the ER membrane, demonstrating that UFMylation is necessary for releasing SEC61 from 60S subunits. Notably, this release is facilitated by a functional switch of UREL from a ‘writer’ to a ‘reader’ module that recognizes its product—UFMylated 60S ribosomes. Collectively, we identify a fundamental role for UREL in dissociating 60S subunits from the SEC61 translocon and the basis for UFMylation in regulating protein homeostasis at the ER.</p

The UFM1 E3 ligase recognizes and releases 60S ribosomes from ER translocons

Stalled ribosomes at the endoplasmic reticulum (ER) are covalently modified with the ubiquitin-like protein UFM1 on the 60S ribosomal subunit protein RPL26 (also known as uL24) 1,2. This modification, which is known as UFMylation, is orchestrated by the UFM1 ribosome E3 ligase (UREL) complex, comprising UFL1, UFBP1 and CDK5RAP3 (ref. 3). However, the catalytic mechanism of UREL and the functional consequences of UFMylation are unclear. Here we present cryo-electron microscopy structures of UREL bound to 60S ribosomes, revealing the basis of its substrate specificity. UREL wraps around the 60S subunit to form a C-shaped clamp architecture that blocks the tRNA-binding sites at one end, and the peptide exit tunnel at the other. A UFL1 loop inserts into and remodels the peptidyl transferase centre. These features of UREL suggest a crucial function for UFMylation in the release and recycling of stalled or terminated ribosomes from the ER membrane. In the absence of functional UREL, 60S–SEC61 translocon complexes accumulate at the ER membrane, demonstrating that UFMylation is necessary for releasing SEC61 from 60S subunits. Notably, this release is facilitated by a functional switch of UREL from a ‘writer’ to a ‘reader’ module that recognizes its product—UFMylated 60S ribosomes. Collectively, we identify a fundamental role for UREL in dissociating 60S subunits from the SEC61 translocon and the basis for UFMylation in regulating protein homeostasis at the ER.</p